Funding SummaryThis funded project, led by Dr. Cai, will look at the problems in satiety (the feeling of being full) signaling in a mouse model of PWS. Dr. Cai thinks that a specific set of neurons in the amygdala region of the brain do not receive or respond to satiety signals properly, and that is why the appetite suppression in PWS is impaired. He will use cutting edge methods to investigate this hypothesis.
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Prader–Willi Syndrome (PWS) is a genetic disorder characterized by insatiable appetite and development of morbid obesity later in childhood. However, the level of satiety signals such as the cholecystokinin secreted from the gut after a meal is not different between PWS and control subjects, suggesting that the brain mechanism detecting satiety signals is impaired and fails to convert satiety signals to feeding suppression in PWS. The neural mechanism underlying appetite control in PWS is still poorly understood. Using novel genetic methods, we recently discovered that a specific type of neurons in a brain region called central amygdala are activated by satiety signals, silencing these neurons blocks the feeding suppression caused by satiety signals and activation of these neurons suppresses feeding. These results suggest that these central amygdala neurons are both necessary and sufficient for appetite suppression during satiety. In this proposal, we will use PWS animal models, in vivo calcium imaging and combination of multiple cutting-edge approaches to test the hypothesis that the response of these neurons to appetite-suppression signals are impaired in PWS and thereby cannot convert the signals to feeding suppression. The expected outcomes are that we will identify the impaired brain mechanism for appetite-suppression signals in PWS. The next step is to determine if the central amygdala neurons could potentially be targeted to control appetite in PWS. This project will help us understand how satiety and appetite are regulated in the brain of PWS, suggest novel druggable targets for the development of therapeutic approaches or interventions to treat insatiable appetite and hyperphagia in PWS.
Research Outcomes: PublicationsNeural Circuit Mechanism Underlying the Feeding Controlled by Insula-Central Amygdala Pathway. Zhang-Molina C, Schmit MB, Cai H. Cell Press (2020), 23 (4); 101033.
Haijing Cai, Ph.D.
University of Arizona
Haijing Cai, Ph.D.